Oxidized glutathione (GSSG) is useful in fields of health foods, pharmaceuticals, cosmetics, fertilizers and the like as well as reduced glutathione (GSH). For example, it is known that oxidized glutathione has detoxication or the like (Non-patent Document 1 and others).
Oxidized glutathione (GSSG) has a molecular structure obtained by oxidizing two molecules of reduced glutathione (GSH) to form a disulfide bond, and reduced glutathione is a tripeptide composed of glutamic acid, cystein and glycine, that is, “L-γ-glutamyl-L-cysteinyl-glycine”.
As a method for producing oxidized glutathione, for example, there is known a method for producing oxidized glutathione in the form of an aqueous solution by first preparing an aqueous solution or yeast extract containing reduced glutathione with a fermentation method, and oxidizing the aqueous solution or yeast extract (Patent Document 1, Patent Document 2 and others). The oxidized glutathione obtained in the above-mentioned manner is powdered as an oxidized glutathione-containing yeast extract powder by, for example, adding an excipient or the like to the aqueous solution, followed by freeze-drying or spray-drying. However, depending on the uses thereof, it may not be allowed to use an excipient and use of an excipient may be limited in some cases.
Conventionally, as the oxidized glutathione which is obtained in the form of a solid without using an excipient, for example, a powder of oxidized glutathione anhydride is known. Such a powder is obtained by separating and purifying oxidized glutathione from the above-described aqueous solution of oxidized glutathione, followed by freeze-drying, spray-drying or the like. In addition, three forms of oxidized glutathione are known, that is, oxidized glutathione hydrate and oxidized glutathione salt in addition to the anhydrate. However, the forms of oxidized glutathione have various problems in terms of industrial uses.
For example, oxidized glutathione anhydride has a problem of having extremely high hygroscopicity and deliquescency. In order to avoid moisture absorption and deliquescence, for example, the anhydride is required to be cooled or frozen, or alternatively kept in a specially wrapped state for preventing moisture absorption at the time of preservation, transportation, distribution and the like. In any cases, the anhydride is unsuitable for large supply in an industrial level. In addition, the anhydride is highly water-soluble so that the anhydride is used for an aqueous solution product such as a medical agent for injection, but is easy to be converted into hydrate in water. The hydrate has low solubility in water, and there is a risk that the crystal thereof is precipitated in the aqueous solution product.
As oxidized glutathione hydrate, a crystal of oxidized glutathione octahydrate (Non-patent Document 2) and a crystal of oxidized glutathione monohydrate (Patent Document 3) are known. A crystal of oxidized glutathione octahydrate easily releases crystal water and is difficult to keep the water amount in the crystal at a constant level and thus inferior in stability. Also, the octahydrate is insufficient in reproduction and unsuitable for large-scale synthesis or industrialization. A crystal of oxidized glutathione monohydrate is low deliquescent; on the other hand, the monohydrate is difficult to be handled in the form of an aqueous solution owing to low solubility in water, and thus it is impossible to produce an aqueous solution product of the monohydrate with a high concentration. In addition, when oxidized glutathione is produced, a base is generally used and it is necessary to remove the base in order to precipitate the monohydrate. Therefore, it is required to use, for example, an ion exchange resin or a chelating resin. However, in the case of the treatment with such resins, environmental burdens, such that a large quantity of a waste solution is generated and the treatment therefor is required, are increased, and there is a problem in terms of the cost.
As an oxidized glutathione salt, salts of a metal and an amino acid are known. As a metal salt of oxidized glutathione, an oxidized glutathione disodium salt is commercially available and additionally an alkali metal salt such as a dilithium salt of oxidized glutathione (Patent Document 4) is known. In addition, an amino acid salt such as a monoornithine salt of oxidized glutathione (Patent Document 5) and a monolysine salt of oxidized glutathione (Patent Document 6) are so far reported. However, there are few examples of being isolated. An alkali metal salt of oxidized glutathione such as a disodium salt of oxidized glutathione and a dilithium salt of oxidized glutathione is difficult to be made available in the form of a solid in the first place. In addition, such an alkali metal salt has extremely high deliquescency and is unsuitable for industrial use similarly to oxidized glutathione anhydride. Further, with respect to an amino acid salt such as a monoornithine salt of oxidized glutathione and a monolysine salt of oxidized glutathione, for example, there is a problem that the amino acid salt has the same functional group as that of oxidized glutathione, and therefore the amino acid causes a competitive reaction to inhibit the aimed reaction when the salt is subjected to the reaction. In addition, there is another problem that an amino acid is physiologically active substance, and therefore addition of the salt to a final product is often limited.